Plasma Biomarkers of Acute Respiratory Distress Syndrome Vary with Body Size in the Absence of Acute Illness
- 1Mass General Brigham
Abstract
RationalePlasma proteins are used as biomarkers of inflammation and injury in acute respiratory distress syndrome (ARDS). Whether they vary with body size before ARDS is not well established.
ObjectivesTo determine whether ARDS biomarkers vary with body mass index in adults without acute illness.
MethodsWe analyzed 8,680 ambulatory adults in a cross sectional study of the All of Us Research Program with proteomics covering 5,420 protein assays. We grouped 35 proteins associated with ARDS risk or mortality into five compartments by the pathophysiological role assigned in a published systematic review, registered in advance. We modeled body mass index as a restricted cubic spline and reported the difference in each protein between 35 and 25 kg/m2 in standard deviations, adjusted for age, sex, smoking, thirteen chronic conditions and ten genetic principal components. Each estimate was ranked against all 5,420 assays.
ResultsMedian age was 50 years and median body mass index 27.2 kg/m2. Associations with body mass index across all assays were predominantly positive, median 0.065 standard deviations. All four epithelial proteins were lower at higher body mass index, each below at least 92% of assays. Soluble receptor for advanced glycation end products was lower by 0.350 standard deviations and surfactant protein A2, surfactant protein D and club cell secretory protein 16 were lower by 0.081 to 0.084 standard deviations. Interleukin-6 and E-selectin were 0.534 and 0.465 standard deviations higher, above 99% of assays. Differences across body mass index extended to lung enriched proteins outside the 35. Compartments accounted for 49% of the variance in the 35 protein estimates, against 10% under random reassignment (P < 0.001). At fixed body mass index, type 2 diabetes, hypertension and dyslipidemia showed smaller differences in ARDS biomarkers and were not associated with lower epithelial proteins.
ConclusionsPlasma proteins used as biomarkers of inflammation and injury in ARDS vary with body size even in the absence of acute illness. Differences during ARDS may not be attributable to injury alone and may be misinterpreted in patients with obesity due to antecedent variation.
Related
- Diagnostic Performance of the Radiographic Assessment of Lung Edema Score for Acute Respiratory Distress Syndrome-Post Hoc Analysis of the "Validating Acute Lung Injury Biomarkers for Diagnosis" Study.
- Nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as initial respiratory support during minimally invasive surfactant therapy in preterm infants with respiratory distress syndrome: a retrospective real-world cohort study
- Respiratory Distress Syndrome: An Important Risk Factor for Intraventricular Hemorrhage in Preterm Neonates
- Global Protective Ventilator Settings Are Not Regional Protection: A Compartment-Resolved Framework for Personalizing Mechanical Ventilation in Acute Respiratory Distress Syndrome
- Downregulation of alcohol dehydrogenase family proteins suggests disrupted retinol metabolism in neonatal respiratory distress syndrome: an umbilical cord blood proteomics study
BibTeX
@misc{gaulton2026plasma,
title = {{Plasma Biomarkers of Acute Respiratory Distress Syndrome Vary with Body Size in the Absence of Acute Illness}},
author = {T. G. Gaulton and L. Berra and M. Cereda},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.19.26362333},
url = {https://www.medrxiv.org/content/10.64898/2026.09.19.26362333v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Plasma Biomarkers of Acute Respiratory Distress Syndrome Vary with Body Size in the Absence of Acute Illness
AU - T. G. Gaulton
AU - L. Berra
AU - M. Cereda
PY - 2026
DA - 2026/09/19
PB - medRxiv
DO - 10.64898/2026.09.19.26362333
UR - https://www.medrxiv.org/content/10.64898/2026.09.19.26362333v1
AB - RationalePlasma proteins are used as biomarkers of inflammation and injury in acute respiratory distress syndrome (ARDS). Whether they vary with body size before ARDS is not well established. ObjectivesTo determine whether ARDS biomarkers vary with body mass index in adults without acute illness. MethodsWe analyzed 8,680 ambulatory adults in a cross sectional study of the All of Us Research Program with proteomics covering 5,420 protein assays. We grouped 35 proteins associated with ARDS risk or mortality into five compartments by the pathophysiological role assigned in a published systematic review, registered in advance. We modeled body mass index as a restricted cubic spline and reported the difference in each protein between 35 and 25 kg/m2 in standard deviations, adjusted for age, sex, smoking, thirteen chronic conditions and ten genetic principal components. Each estimate was ranked against all 5,420 assays. ResultsMedian age was 50 years and median body mass index 27.2 kg/m2. Associations with body mass index across all assays were predominantly positive, median 0.065 standard deviations. All four epithelial proteins were lower at higher body mass index, each below at least 92% of assays. Soluble receptor for advanced glycation end products was lower by 0.350 standard deviations and surfactant protein A2, surfactant protein D and club cell secretory protein 16 were lower by 0.081 to 0.084 standard deviations. Interleukin-6 and E-selectin were 0.534 and 0.465 standard deviations higher, above 99% of assays. Differences across body mass index extended to lung enriched proteins outside the 35. Compartments accounted for 49% of the variance in the 35 protein estimates, against 10% under random reassignment (P < 0.001). At fixed body mass index, type 2 diabetes, hypertension and dyslipidemia showed smaller differences in ARDS biomarkers and were not associated with lower epithelial proteins. ConclusionsPlasma proteins used as biomarkers of inflammation and injury in ARDS vary with body size even in the absence of acute illness. Differences during ARDS may not be attributable to injury alone and may be misinterpreted in patients with obesity due to antecedent variation.
ER -